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000136826 0247_ $$2doi$$a10.1016/j.lfs.2013.01.010
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000136826 0247_ $$2ISSN$$a0024-3205
000136826 0247_ $$2ISSN$$a1879-0631
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000136826 037__ $$aDZNE-2020-03148
000136826 041__ $$aEnglish
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000136826 1001_ $$0P:(DE-2719)2810511$$aHaenisch, Britta$$b0$$eFirst author
000136826 245__ $$aInvestigation into mechanisms mediating the inhibitory effect of 1,4-benzodiazepines on mast cells by gene expression profiling.
000136826 260__ $$aNew York, NY [u.a.]$$bElsevier Science$$c2013
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000136826 520__ $$aThis study aims to identify by a molecular genetic approach potential targets in mast cells at which 1,4-benzodiazepines may cause their inhibitory effect on mast cell activity.Gene expression analyses with microarray gene chip and/or quantitative PCR were performed using 1,4-benzodiazepine-treated human mast cell leukemia HMC-1.2 cells, promyelocytic leukemia HL-60 cells and human mast cells from healthy volunteers and patients with mast cell activation disease (MCAD). Pathway analysis was applied to search for enriched biological functions and canonical pathways within differentially regulated genes.Both neoplastic and normal human mast cells express several GABA(A) receptor subunits at the mRNA level. In mast cells from MCAD patients expression of some GABA(A) receptor subunits and expression of the translocator protein TSPO are increased compared with those from healthy controls. Expression of the protein tyrosine kinases Lyn, Fgr and Yes1 was increased in HMC-1.2 cells as compared with the ontogenetically related HL60 cells. Differences in gene regulation in HMC-1.2 cells after treatment with the 1,4-benzodiazepines clonazepam, flunitrazepam and 4-chlorodiazepam suggested that signaling and gene expression induced by clonazepam was similar to that of flunitrazepam but different from that of 4-chlorodiazepam. This conclusion is supported by the results of the pathway analysis.A novel type of GABA(A) receptors on mast cells appears to be involved in the inhibition of mast cell activity by 1,4-benzodiazepines. These receptors seem to be composed without γ subunits suggesting unique pharmacological properties. An action at Src-kinases, or at TSPO located in the plasma membrane may also be involved.
000136826 536__ $$0G:(DE-HGF)POF3-345$$a345 - Population Studies and Genetics (POF3-345)$$cPOF3-345$$fPOF III$$x0
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000136826 650_7 $$2NLM Chemicals$$aBenzodiazepinones
000136826 650_7 $$02QW0IK1742$$2NLM Chemicals$$a4'-chlorodiazepam
000136826 650_7 $$05PE9FDE8GB$$2NLM Chemicals$$aClonazepam
000136826 650_7 $$0620X0222FQ$$2NLM Chemicals$$aFlunitrazepam
000136826 650_2 $$2MeSH$$aAdult
000136826 650_2 $$2MeSH$$aAged
000136826 650_2 $$2MeSH$$aBenzodiazepinones: pharmacology
000136826 650_2 $$2MeSH$$aClonazepam: pharmacology
000136826 650_2 $$2MeSH$$aFemale
000136826 650_2 $$2MeSH$$aFlunitrazepam: pharmacology
000136826 650_2 $$2MeSH$$aGene Expression: drug effects
000136826 650_2 $$2MeSH$$aGene Expression Profiling: methods
000136826 650_2 $$2MeSH$$aHL-60 Cells
000136826 650_2 $$2MeSH$$aHumans
000136826 650_2 $$2MeSH$$aMale
000136826 650_2 $$2MeSH$$aMast Cells: drug effects
000136826 650_2 $$2MeSH$$aMastocytosis: genetics
000136826 650_2 $$2MeSH$$aMicroarray Analysis: methods
000136826 650_2 $$2MeSH$$aMiddle Aged
000136826 650_2 $$2MeSH$$aPolymerase Chain Reaction: methods
000136826 7001_ $$0P:(DE-HGF)0$$aHuber, Michael$$b1
000136826 7001_ $$0P:(DE-HGF)0$$aWilhelm, Thomas$$b2
000136826 7001_ $$0P:(DE-HGF)0$$aSteffens, Michael$$b3
000136826 7001_ $$0P:(DE-HGF)0$$aMolderings, Gerhard J$$b4$$eCorresponding author
000136826 77318 $$2Crossref$$3journal-article$$a10.1016/j.lfs.2013.01.010$$b : Elsevier BV, 2013-03-01$$n6-7$$p345-351$$tLife Sciences$$v92$$x0024-3205$$y2013
000136826 773__ $$0PERI:(DE-600)2013911-1$$a10.1016/j.lfs.2013.01.010$$gVol. 92, no. 6-7, p. 345 - 351$$n6-7$$p345-351$$q92:6-7<345 - 351$$tLife sciences$$v92$$x0024-3205$$y2013
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